This collaborative team aims to build on previous research by uncovering novel selective modulators of the human D2 dopamine receptor. During this period, the NCGC has pursued a medicinal chemistry campaign on the lead chemotypes to characterize their structure-activity relationships and further improve their potency and properties. The team has identified two new exquisitely selective D2R antagonist series. Following extensive optimization, one series is currently under evaluation in several advanced animal models. The second series is still under optimization to further improve its pharmacokinetic properties.